Clinical Spectrum of Pediatric Heat Illness and Heatstroke in a North American Desert Climate.

ABSTRACT: The spectrum of historical features and clinical presentations of heat illness and heatstroke in the pediatric population has received limited focus in the emergency medicine literature. The majority of published cases involve children trapped in closed spaces and adolescent athletes undergoing high-intensity training regimens in geographical regions with moderately high ambient temperatures and high humidity. There has been less research on the potential impact of extreme temperatures and radiant heat that are the hallmarks of the US southwest region. We performed a retrospective review of pediatric heat illness at our facility located in a North American desert climate.

Fatal Cerebral Vasospasm following a Haemophilus influenzae Meningitis in a Young Child with Ventriculoperitoneal Shunt.

INTRODUCTION: Despite the successful implementation of Haemophilus influenzae vaccination, invasive serotypes still lead to a fatal infection. We recently cared for a patient with a ventriculoperitoneal shunt (VPS) and H. influenzae meningitis and septicemia complicated by vasospasm. Vasospasm caused by Haemophilus central nervous system infection has not been previously reported. CASE PRESENTATION: A 34-month-old patient with a recent VPS presented with H. influenzae meningitis and sepsis. Despite the explant of hardware, followed by maximum medical management, the patient developed stroke due to severe vasospasm, which led to diffused anoxic brain injury. CONCLUSIONS: We aim to alert for the possible critical condition caused by H. influenzae. It is essential to treat the underlying illness, despite the presence of a VPS. Surgical implant tends to be overlooked by other subspecialists. Being vaccinated to H. influenzae does not protect from different subtypes like non-typeable H. influenzae. The cause of vasospasm remains unclear.

TGFbeta1 induces mast cell apoptosis.

Mast cells are potent effectors of the inflammatory response, playing an important role in atopy, bacterial immunity, and animal models of arthritis, multiple sclerosis, and heart disease. Hence controlling mast cell numbers and responsiveness is essential for preventing inflammatory disease. We demonstrate that the cytokine transforming growth factor (TGF) beta1 is a potent inducer of mast cell apoptosis, a finding that was consistent in cultured mouse bone marrow-derived mast cells, peritoneal mast cells, and human mast cells. Cell death appeared to be caused by TGF-mediated repression of interleukin-3 (IL-3) receptor expression and function, leading to mitochondrial damage and activation of an apoptotic cascade acting via p53 and caspases. Although IL-3 receptor expression was reduced within 1 day of TGFbeta1 stimulation, apoptosis required at least 3 days to occur. This delay in onset is postulated to allow protective mast cell effector functions, protecting the host from infection while preventing the establishment of chronic inflammation. Our data support the theory that TGFbeta1 is an inhibitor of mast cell survival. The widespread expression of TGFbeta1 offers this cytokine as an ideal candidate for control of mast cell homeostasis.

IFN-gamma induces apoptosis in developing mast cells.

Mast cells are critical effectors of allergic disease, and are now implicated in immune responses observed in arthritis, multiple sclerosis, and heart disease. Because of their role in inflammation, understanding how mast cells develop is of clinical importance. In this study we determined the effects of IFN-gamma on mast cell survival. Using in vitro culture of bone marrow cells in IL-3 plus stem cell factor, we found that the addition of IFN-gamma induced apoptosis, as exhibited by the presence of subdiploid DNA and caspase activation. IFN-gamma-mediated apoptosis was Stat1-dependent, and was accompanied by loss of mitochondrial membrane potential. Apoptosis was reduced in cultures of bone marrow cells derived from p53- or Bax-deficient mice, as well as H2K-Bcl-2 transgenic mice. IFN-gamma hyperresponsiveness has been shown to result in inflammatory disease and death in mice lacking the regulatory protein suppressor of cytokine signaling (SOCS)-1. Bone marrow cells from SOCS-1 knockout (KO) mice failed to give rise to viable mast cells after culture in IL-3 plus stem cell factor, with profound apoptosis occurring as the cultures matured. However, bone marrow cells lacking both SOCS-1 and IFN-gamma survived normally. This in vitro defect in mast cell development was recapitulated in vivo. SOCS-1 KO mice demonstrated a 67% decrease in peritoneal mast cell numbers relative to wild-type mice, a deficiency that was reversed in SOCS-1/IFN-gamma KO mice. These data demonstrate the potent regulatory effects of IFN-gamma on mast cell survival and show that this cytokine can elicit mast cell death in vitro and in vivo.

TGF-beta 1 inhibits mast cell Fc epsilon RI expression.

Mast cell activation through the high affinity IgE receptor (FcepsilonRI) is a critical component of atopic inflammation. The cytokine TGF-beta1 has been shown to inhibit IgE-dependent mast cell activation, possibly serving to dampen mast cell-mediated inflammatory responses. We present proof that TGF-beta1 inhibits mast cell FcepsilonRI expression through a reversible pathway that diminishes protein, but not mRNA, expression of the FcepsilonRI subunit proteins alpha, beta, and gamma. The stability of the expressed proteins and the assembled cell surface complex was unaltered by TGF-beta1 treatment. However, TGF-beta1 decreased the rate of FcepsilonRI beta-chain synthesis, arguing that this inhibitory cytokine exerts its effects at the level of mRNA translation. TGF-beta1 consistently diminished FcepsilonRI expression on cultured human or mouse mast cells as well as freshly isolated peritoneal mast cells. The related cytokines, TGF-beta2 and TGF-beta3, had similar effects. We propose that TGF-beta1 acts as a negative regulator of mast cell function, in part by decreasing FcepsilonRI expression.